Links between T cell clonotypes, as defined by T cell receptor (TCR) sequences, and phenotype, as reflected in gene expression (GEX) profiles, surface protein expression and peptide:major histocompatibility complex binding, can reveal functional relationships beyond the features shared by clonally related cells. Here we present clonotype neighbor graph analysis (CoNGA), a graph theoretic approach that identifies correlations between GEX profile and TCR sequence through statistical analysis of GEX and TCR similarity graphs. Using CoNGA, we uncovered associations between TCR sequence and GEX profiles that include a previously undescribed ‘natural lymphocyte’ population of human circulating CD8⁺ T cells and a set of TCR sequence determinants of differentiation in thymocytes. These examples show that CoNGA might help elucidate complex relationships between TCR sequence and T cell phenotype in large, heterogeneous, single-cell datasets.

由 T 细胞受体 (TCR) 序列定义的 T 细胞克隆型和反映在基因表达 (GEX) 谱、表面蛋白表达和肽：主要组织相容性复合物结合中的表型之间的联系，可以揭示超出共同特征的功能关系克隆相关的细胞。在这里，我们提出克隆型邻域图分析 (CoNGA)，这是一种图论方法，通过 GEX 和 TCR 相似性图的统计分析来识别 GEX 配置文件和 TCR 序列之间的相关性。使用 CoNGA，我们发现了 TCR 序列和 GEX 谱之间的关联，其中包括以前未描述的人类循环 CD8 ^{+的“天然淋巴细胞”群体}T细胞和一组胸腺细胞分化的TCR序列决定因素。这些例子表明，CoNGA 可能有助于阐明大型、异质、单细胞数据集中的 TCR 序列和 T 细胞表型之间的复杂关系。